The spore forming bacterium Clostridium Difficile (C. diff.) is known to cause a variety of problems in the human body and particularly in the human digestive system. The bacterium in its spore form is extremely resilient to antimicrobial agents as well as other forms of chemical and physical treatments. These C. diff. spores are capable of surviving the harsh acidic conditions within the stomach and can end up in the intestines of the body.
Once in the intestine, typically the large intestine, C. diff. spores are able to germinate into the more active bacterial species which secretes harmful toxins which cause illness such as pseudo-membranous colitis or even toxic megacolon.
In order to destroy such spores outside the body, for example where the spores are present on surfaces, strong chemical cleaning agents such as bleach are required. This is undesirable as such cleaning agents (often used in high concentrations) are more difficult to handle compared to standard antibacterial treatments and also can not be used on the skin.
However, the most significant problem with C. diff. infection appears to be where a patient has contracted another, accompanying bacterial infection and is treated with antibiotics, especially broad-spectrum antibiotics. The antibiotics destroy not only the target bacteria for which the antibiotics were prescribed, but also significantly reduce the amount of bacteria present in the gut. As C. diff. in its spore form typically resist attack by antibiotics, this leads to a situation where C. diff. spores can enter the gut, germinate into the more active bacterial species, and can thrive as there is little in the way of competition from native gut bacteria.
These problems mean that C. diff. can be a significant problem in hospitals and healthcare facilities where many patients are undergoing or have recently completed a course of antibiotics and where healthcare professions, although diligent in their use of antimicrobial cleaning products to destroy conventional microbes present on their person in between patient interactions, may still transmit C. diff. spores to many individuals.
Current treatments for C. diff. infections include administration of antibiotics but patients often experience relapses, possibly because the antibiotics are only capable of treating the germinated C. diff. bacteria not any residual ungerminated spores. Alternative treatments include performing a stool transplant in order to re-establish the bacterial environment of the gut, thereby reducing the amount of C. diff. bacteria due to increased competition for nutrients with the transplanted bacteria. However, this procedure is not an attractive option for many patients.
Extensive research has been performed to examine what causes germination of C. diff. spores. Wilson K (J. Clin Microbial 1983 1017-1019) states that the presence of certain bile salts appears to trigger germination of C. diff. spores in the large intestine. Other sources such as Sorg J A and Sonenshein A L (J. Bacteriol 2008, 2505-2512) states that both bile salts and certain amino acids play an important role in bringing about germination of C. diff. spores. There has also been some research into compounds which act as inhibitors to the germination of C. diff. spores. Sorg J A and Sonenshein A L (J. Bacteriol 2010, 4983-4990) for instance, discloses various compounds found to reduce the rate of germination of C. diff. spores.
Accordingly, what is required is a method of treating C. diff. spores in vivo as well as methods for preventing the spread of C. diff. spores ex vivo, particularly in healthcare environments.
The invention is intended to overcome or at least ameliorate some of the problems outlined above.